The fundamental challenge of radiotherapy is to treat cancer patients effectively and safely. Current radiotherapy systems and methods provide excellent benefits for patients with early stage and radiosensitive cancers, but these benefits diminish for patients with radioresistant tumors (e.g., brain or pancreas cancers) and patients with late stage tumors. For these patients, the radiation needed to eradicate the tumor can cause intolerable or fatal radiation damage. This is especially the case for pediatric patients, whose rapidly developing normal tissues are often more radiosensitive than their tumors, and who therefore cannot tolerate radiotherapy that would be curative for adults with the same disease. As a result, normal tissue collateral damage is a major limitation in current radiotherapy, preventing effective radiotherapy treatments for cancer patients of a young age, patients with central nerve system cancers, radioresistant cancers, and late stage cancer with large tumors. These cancer patients currently have a poor prognosis.
Microbeam Radiotherapy (MRT) is a unique form of radiation that has shown an extraordinary ability to eradicate tumors while sparing normal tissue in numerous animal studies. MRT utilizes multiple narrow but well separated x-ray planar beams (i.e., “microbeams”) and delivers radiation at extremely high dose rate. MRT radiation differs from conventional radiotherapy radiations in two aspects: dose spatial discreteness and dose temporal rate. In conventional therapy, the dose rate is about 100 times lower and the dose distribution is microscopically continuous in space. The current solution, which is not always effective, is to use multiple treatments at 2 Gy per treatment. In contrast, animal studies have shown that single treatments at a dose level of several hundred Gy (e.g., about 102 Gy or greater) can eradicate a tumor while sparing normal tissue, including developing tissue in the central nervous system.
There are currently two hypotheses for the mechanism by which MRT can provide tumor eradication while sparing normal tissue. First, it is believed that tumor microvasculature does not repair itself well while normal tissue does. Second, there appears to be a bystander effect wherein unirradiated tumor cells die with irradiated tumor cells through cell-cell signaling (See, e.g., D. Slatkin et al., Proc. Natl. Acac. Sci. USA, Vol 92, pp 8783-8787, 1995). However, the underlying mechanism of MRT is still poorly understood. Nonetheless, MRT is extremely attractive for human application as the key challenge of radiotherapy has been how to eradicate tumors with minimal collateral damage to the host normal tissue.
Unfortunately, however, MRT requires that x-rays with an extremely high dose rate (e.g., on the order of 100 Gy/s or higher) are needed to irradiate tissues in a fraction of a second to assure minimal broadening of the micro slices due to movement of the target. This dose rate is several orders of magnitude higher than what is typically used for conventional radiation therapy.
Existing x-ray tube technologies today cannot provide a MRT dose distribution and dose rate as the MRT dose rate can be thousands of times that of state-of-art radiotherapy machines (˜5 Gy/min). The high dose rate is thought to be important for minimizing the broadening (due to the object motion) of the tens of micron wide microbeam required during irradiation of live objects. A conventional x-ray tube comprises a metal filament (cathode) which emits electrons when it is resistively heated to over 1000° C. and a metal target (anode) that emits x-ray when bombarded by the accelerated electrons. The spatial resolution of an x-ray source is determined by the size of the focal spot which is the area on the x-ray anode that receives the electron beam. Because of the high operating temperature and power consumption, essentially all current commercial x-ray tubes are single-pixel devices where x-ray radiations are emitted from single focal spots on the anodes. The heat load of the anode limits the maximum x-ray flux of an x-ray tube. To generate the small MRT beam size at the ultrahigh dose rate using the current x-ray technology would require an ultrahigh electron beam density and heat load that are beyond physical possibility. For instance, the state-of-art high-power x-ray tube operating at ˜100 kW delivers only about 1-10 cGy/s at patient with ˜0.6 m source-object distance
As a result, due to this high required dose rate, MRT has thus far been studied exclusively using synchrotron radiation, for instance at the National Synchrotron Light Source (NSLS) in the United States and at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France. Therefore, in order to speed up the research that may advance the promising cancer treatment for potential human application, there is a need for compact, non-synchrotron source MRT systems and associated methods that can be widely available for cancer centers for preclinical research and clinical application.